Will the Gene Microscope Change the World?

Clifford Reid predicts a paradigm shift in genome sequencing.

By Allison Proffitt

May 19, 2009 | BOSTON—The invention of the light microscope in 1590 advanced many scientific disciplines, but medicine, curiously wasn’t one of them. Three hundred years later, a series of closely timed microscope advancements proved the tipping point and tuberculosis was all but eradicated in three years.

“We’re building gene microscopes,” said Complete Genomics’ CEO Clifford Reid. “With this technology and the computer technology available to us, we’re going to change the world.”

In the final keynote, Reid attributed the genome sequencing explosion to the recent arrival of a series of disruptive technologies. “The slope of the line changed from 2x a year improvement [in sequencing costs], to 10x a year improvement. And the price of human genome sequencing began to collapse. Now if you extend that line… you’ll realize that you’ll be able to get your genome sequenced in 2015 for one penny. This will not happen, I assure you.”

Reid pointed to three areas of technology that have prompted the disruption: bio, nano, and info.

“In the bio area, molecular tools have exploded in the past five years; they have become extraordinary,” he said, citing advancements in oligos, DNA amplification, fluorescent chemistry, and enzymology. “Coupled with that, we have this massive revolution in nano tools,” including photolithography, robotics, and optical systems that are inexpensive, high quality, and innovative. Finally, “the revolution that we’ve all been living with… is the info technology revolution. There’s been a fundamental informatic insight into DNA sequencing around paired end sequencing.”

The last insight is one on which Complete Genomics has built their business. They start by circularizing a DNA fragment, adding read addresses at regular intervals around the circle, and then amplify the DNA into nanoballs (see, “Complete Genomics…” Bio•IT World, Nov 2008). “The extraordinary thing about this amplification strategy is that it takes place in a test tube to amplify a genome’s worth of sequence in about 20 minutes, and at today’s enzyme prices costs about $27.”

From there, the DNA is dropped onto a slide to be read with fluorescent chemistry. Currently, Complete Genomics can read about 10% of a human genome sequence on a single slide in about a day and a half. “To read the next generation of slides that will be in commercial production by this time next year, it will take a half a day. Half a day to read a complete human genome worth of DNA.”
Whereas chemistry costs used to drive the industry, Reid said that had changed. Today, the limiting factors are visualization and compute power.

Paradigm Shift
With these disruptive advancements, Reid sees a paradigm shift happening in the life sciences. “We can afford large scale human sequencing,” he says. The old paradigm produced gigabytes of data that could be analyzed with a single computer. Now genomes consist of 60 terabytes of data and require high performance computing for assembly.

The new paradigm calls for new vendor and user models that CGI is spearheading. CGI will be offering information services, not a box. Sequencing should be scaled up to continuous production. Users, on the other hand, will outsource data generation so they can focus on data analysis and interpretation. In this way, CGI will be a wholesaler of complete human genomics to multiple users, and plans ten centers around the world with the goal of sequencing 1 million human genomes in the next five years.

Reid’s vision opens doors for large-scale studies in functional genomics, orphan disease research by academia, and cancer research. In the past, we were instrument-centric, Reid said. Today we’re data-centric, and in the future we will be action-centric, finally realizing personalized diagnostics and personalized therapeutics.

The technology is now light years beyond the light microscope.

This article also appeared in the May-June 2009 issue of Bio-IT World Magazine.
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